FlyTitle: Metabolites and you

People leave molecular wakes that may give away their secrets

你的分子“尾流”可能会泄露你的秘密

经济学人双语版-海量化学物质 Shed-loads of chemicals

GENES CAN tell tales about you, from who your ancestors were to how likely you are to develop a range of diseases. And it seems probable that in the future they will tell more: your personality type, perhaps, or your intelligence. For these reasons, many countries have laws limiting what use employers and insurance companies can make of such information. America, for example, has the Genetic Information Nondiscrimination Act, which makes it illegal for health insurers and employers to use genetic information to discriminate against customers and employees.

基因可以泄露你的隐私,包括你的祖先是谁,你患各种疾病的几率多大等等。而且未来可能还会泄露更多信息,比如你的性格类型,或者智力水平。正因如此,很多国家都制定了相关法律,限制雇主和保险公司对遗传信息的使用。例如,美国的《遗传信息反歧视法案》(Genetic Information Nondiscrimination Act)规定,医疗保险公司和雇主利用遗传信息区别对待客户和雇员是非法行为。

There is much, however, that genes cannot reveal. They are blind to what you eat, how you exercise, how safe the place you live in is, how you unwind at the end of the day and which god you worship. Just as well, you might think, considering how easy it is to obtain samples of DNA from saliva, sweat or hair, and how cheap it is becoming to analyse such samples. But it is not just DNA that people scatter to the wind as they go about their business. They shed a whole range of other chemicals as well, in their breath, their urine, their faeces and their sweat. Collectively, and somewhat inaccurately, these molecules are referred to as metabolites. Some truly are the products of metabolic activity within people’s bodies. Others are substances an individual has come into contact with, or consumed or inhaled. All, though, carry information of one sort or another.

然而,还是有很多信息无法通过基因获知。基因无法透露你吃了什么,怎样锻炼身体,居住地是否安全,一天下来如何放松自己,以及你信奉哪位神明等等。你可能会觉得,幸好如此,因为要从唾液、汗液或毛发中获取DNA样本简直易如反掌,而且分析这些样本的成本也日益降低。但是,人们在日常活动时,散播到空气中的可不只有DNA。他们还会通过呼吸、尿液、粪便及汗液等排出其他各种化学物质。这些分子被统称为代谢物(尽管可能不太准确)。它们有些确实是人体代谢活动的产物,其他一些则是人们接触、消耗或吸入的物质。不过,所有这些物质都承载着这样或那样的信息。

Blood, tears, sweat and toil

血、泪和汗

Until recently this did not matter much, for two reasons. One was that, in practice, taking samples for analysis required either voluntary collaboration or legal duress. It could not be done clandestinely. The other was that interpreting the complicated patterns of metabolites is hard. But both of these obstacles are now being overcome.

以前这些物质一直无关紧要,但近来情况不同了,原因有二。首先,在实际操作中,采集用于分析的样本要么需要人们自愿配合,要么需要依法强制执行,无法暗中进行。其次,代谢物结构复杂,要分辨清楚并非易事。而现在,这两个关卡都在被攻克。

The most common way of analysing metabolite content is gas chromatography-mass spectrometry. This technique sorts molecules by their weight, producing a pattern of peaks that correspond to different substances. But the same weight can be shared by many molecules, so the results may be ambiguous. Nor, even if a molecule can be identified unambiguously, is its wider significance always obvious to a particular investigator.

分析代谢物成分最常见的方法是气相色谱-质谱法。这种方法根据质量对分子分类,产生一个图谱,其中的各色谱峰与不同的物质相对应。但因为很多分子的质量相同,所以结果可能并不明确。即便分子能被明确地识别出来,某一位研究人员也不总能从中看出更多意义。

There are, however, a lot of information sources out there, in the form of publicly available metabolite databases. And last year a team led by Pieter Dorrestein of University of California, San Diego, invented a way, which they call a metabolite search engine, of linking them up so that a sample can be compared simultaneously with the contents of all of them.

不过,信息来源已有很多,以代谢物数据库的形式开放给公众。去年,加州大学圣迭戈分校的皮耶特·德伦斯坦(Pieter Dorrestein)领导的研究小组发明了一种他们称之为“代谢物搜索引擎”的方法,将这些数据库连接起来,从而可以将一个样本与所有数据库中的所有样本同时加以比对。

The databases themselves are getting better, too. According to Dr Dorrestein, researchers in the field were able, as recently as four years ago, to identify only 2% of the metabolites found in samples. Today, that has increased to 6% and is climbing quickly. “It is reasonable”, he says, “to assume that in another four years we will be able to annotate 20% of the molecular signatures that we encounter, based on the advances that are being made.”

数据库本身也在不断完善。德伦斯坦表示,就在四年前,该领域的研究人员还只能识别出样本中2%的代谢物,如今已经增长到6%,而且正在迅速攀升。他说:“基于目前取得的进展,我们可以合理地认为,再过四年就能识别出所遇到的分子标记物的20%。”

Another area of progress is the type, size and state of preservation of samples that can be interrogated. No longer are blood, urine or breath required. Sweat, tears, saliva and even dental plaque will do. A study just published by Feliciano Priego-Capote at University of Cordoba, in Spain, for example, shows it is possible to extract much meaningful information from even a dried-up drop of sweat—indeed, Dr Priego-Capote is able to find in dried sweat substances that are undetectable at the moment in fresh perspiration.

另外,可分析样本在种类、数量和保存状态等方面都有了进展。样本不再局限于血液、尿液或呼出的气体。汗液、泪水、唾液,甚至牙菌斑都可以。例如,西班牙科尔多瓦大学(University of Cordoba)的费利西亚诺·普里戈-卡波特(Feliciano Priego-Capote)刚刚发表的一项研究表明,即使是一滴干了的汗液,也可能从中提取出很多有意义的信息。普里戈-卡波特甚至能从干掉的汗液中发现在刚排出状态下检测不到的物质。

Such information can reveal a lot. Your god? Regular exposure to burning incense, and thus frequent visits to a church that uses it, will be detectable from the chemicals in the smoke. Not a Christian? Kosher and halal diets are detectable by the absence of metabolites from certain foodstuffs those diets forbid. Your out-of-office activities? Habits like drinking, smoking and narcotic use are visible as numerous chemicals—not merely the active pharmaceuticals which produce the relevant high or low. Your exercise levels? These are flagged up by lower than normal levels of things like leucine, glycerol and phenylalanine. Your local environment? Breathing in polluted air has a marked impact on the profile of your metabolites. Your general health? Illnesses ranging from Parkinson’s disease (altered levels of tyrosine and tryptophan) to diabetes (sugars and sphingomyelin) leave abundant metabolic traces. “The day is coming soon”, observes Cecil Lewis, a molecular anthropologist at University of Oklahoma, who is studying the matter, “when it will be possible to swab a person’s desk, steering wheel or phone and determine a wide range of incredibly private things about them.”

这类信息可以揭示很多东西。你信奉哪位神明?通过探测烟尘中的化学物质,能知道你定期接触焚香,进而知道你经常去使用这种焚香的教堂。你不是基督徒?犹太教和伊斯兰教禁忌的某些食物会让你缺乏某些代谢物,由此可知你是按这些教派的教规饮食。你下班后干了什么?大量化学物质泄露了饮酒、吸烟或吸食毒品的习惯,而不仅仅是带来相应快感或低落情绪的有效药物。你的运动量够不够?亮氨酸、三元醇和苯丙氨酸等物质低于正常水平,就该引起注意了。你居住地的环境怎样?吸入被污染的空气会对你的代谢物档案产生显著影响。你的健康状况大体上如何?各种疾病都会留下大量的代谢痕迹:帕金森病会改变酪氨酸和色氨酸指标,糖尿病会改变血糖和鞘磷脂指标。“很快就会有这么一天,”在俄克拉荷马大学研究这一课题的分子人类学家塞西尔·刘易斯(Cecil Lewis)表示,“用棉签抹一下某个人的办公桌、方向盘或手机,就可能得到关于他方方面面的极为私密的信息。”

Swabbing the decks

一抹便知

In contrast with DNA, the use to which knowledge of metabolites might be put has little legal restriction. Dr Lewis, and others like him, worry about the consequences of this. At the moment, sampling for alcohol or illegal drug use, say, has to be overt, because it involves a blood, urine or breath test. That is true regardless of who is collecting the sample, whether it be the police or an employer. This also keeps purposes clear. A firm might feel it has the right to test employees for drug use, and the law might support that. But techniques like Dr Priego-Capote’s make it easier, as Dr Lewis observes, to sample clandestinely, and bring a temptation to push back the boundaries of what is being searched for. They would, for example, allow companies to detect, if they chose to look, such private matters as whether an employee was taking antidepressants.

相比DNA,对代谢物数据的可能用途还没有什么法律限制。刘易斯和他的同行们都担心这会带来什么后果。比如,由于涉及血液、尿液和呼吸检测,目前对饮酒或服用违禁药物的采样必须公开进行。不管收集样本的是警察还是雇主都一样。这也让采样的目的清楚明白。公司可能认为自己有权检测员工是否吸毒,而法律可能支持它这样做。然而正如刘易斯所说,像普里戈-卡波特研发的那些技术让暗中采样变得更加容易,会诱使一些人扩大搜寻的信息范围。例如,如果公司真要调查员工是否服用抗抑郁药之类的隐私,这些技术就会派上用场。

Metabolite data, even the sort obtained openly, will also be of interest to medical-insurance companies, who may insist on the provision of samples as a condition of the provision of cover. They, too, might take an interest in matters of diet and exercise, penalising those who do not conform to prescribed healthy regimes.

代谢物数据——即使是公开获得的那一类——也会让医疗保险公司感兴趣。它们可能会坚持让客户提供样本,作为投保的必要条件。它们也会关注客户饮食和锻炼的情况,对那些不遵循规定的健康方案的人另眼相待。

The police may be tempted to push the boundaries as well. The fourth amendment to America’s constitution protects against unwarranted searches and seizure of evidence. This means it is hard to force someone to give a sample. But if obtaining such merely requires taking a swab of a surface in a public place—perhaps a keyboard someone has just used—the amendment is unlikely to apply.

警方也可能忍不住要越界执法。美国宪法第四修正案保护公民免受无端的搜查和取证。这意味着很难强迫他人提供样本。但是,如果只需在公共场所擦拭一下某个物体的表面——或许是刚用过的键盘,那么修正案就不大管用了。

That is not necessarily wrong, if it means more criminals are caught and convicted. But it needs to be thought about carefully, because many metabolites are sticky. Cocaine is a case in point. Studies have shown that as many as two-thirds of the dollar bills in circulation in America carry traces of this substance, which might thus end up on the fingertips of the innocent, as well as the guilty.

如果这样做能抓到更多罪犯并给他们定罪,倒也未必是件坏事。但还是需要考虑周全,因为很多代谢物是有黏性的。可卡因就是这样。研究表明,在美国,流通中的美钞有多达三分之二都沾有些许可卡因,所以指尖沾了可卡因的既可能是罪犯,也可能是无辜的人。

Perversely, this might even help someone who really had taken the drug. The law in many jurisdictions permits employers to fire employees for unlawful conduct, even if it happens outside the workplace. But as Michelle Terry of WKS Law in Los Angeles, observes, given how sticky research has shown cocaine metabolites to be, it is hard to guess how the courts would rule if someone lost their job for testing positive, yet claimed never knowingly to have touched the stuff.■

这就可能事与愿违,反倒帮了那些真正的瘾君子。许多司法辖区的法律允许雇主解雇有非法行为的员工,即使这种行为发生在工作场所之外。但是,正如洛杉矶WKS律师事务所(WKS Law)的米歇尔·特里(Michelle Terry)所言,由于研究表明可卡因代谢物的黏性很强,如果有人因为检测结果呈阳性而失业,而他本人却声称从未有意接触过可卡因,很难想象法院会如何判决。

Correction: In “No small matter” (February 1st) we suggested that Charles Lieber’s research at Harvard was connected with Elon Musk’s brain-machine interface project. In fact Neuralink, Mr Musk’s firm, is completely separate from Dr Lieber’s endeavours.

更正:在2月1日的《纳米非小事》(No small matter)中,我们提到查尔斯·李波在哈佛的研究与伊隆·马斯克的脑机接口项目有关。而事实上,马斯克的Neuralink公司与李波的研究毫不相干。